This invention relates to a process for preparing 4-(4-biphenylyl)-4-oxo-butanoic acid useful as drugs and, more particularly, to an improved process for preparing the same by utilization of the Friedel-Crafts reaction in which chlorobenzene is used as a solvent.
4-(4-Biphenylyl)-4-oxo-butanoic acid is known to be a non-steroidal anti-inflammatory and analgesic agent having a low gastric disturbance, which is called "fenbufen" under a general name. As a process for the preparation of this compound, it is known that the process utilizing the Friedel-Crafts reaction is most effective. D. H. Hey, et al., in J. Chem. Soc. 1030 (1940) disclose the preparation of .beta.-p-phenylbenzoylpropionic acid, by adding a mixture of diphenyl and succinic anhydride to a mixture of aluminum chloride and nitrobenzene at 5.degree.-10.degree. C., and standing the mixture for 6 days at room temperature. Likewise, Example 1 of U.S. Pat. No. 3,784,701 illustrates the preparation of 3-(4-biphenylcarbonyl)propionic acid, by dissolving aluminum chloride in nitrobenzene, adding a mixture of succinic anhydride and biphenyl to the solution at a temperature below 10.degree. C., and holding the mixture at room temperature for 4 days. However, such prior art processes suffer from the disadvantages, either technical or economic in the point that nitrobenzene and sym-tetrachloroethane used therein as a solvent have high toxicity and high boiling point, and are more expensive than conventional solvents. In particular, high toxicity of the solvent has involved hazards in the handling thereof and troublesome waste water treating. They also suffer from the disadvantage of requiring long reaction time. Thus, there have been desired improved processes which can be carried out safely and in shorter reaction time.